Division of Allergy Immunology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md.
J Allergy Clin Immunol Pract. 2022 Jun;10(6):1598-1605.e2. doi: 10.1016/j.jaip.2022.02.037. Epub 2022 Mar 10.
Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti-IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology.
To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders.
Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n = 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti-IL-5RA) were assessed before and after treatment (NCT02130882).
Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05).
Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.
先前针对嗜酸性食管炎的靶向嗜酸性粒细胞生物制剂的研究结果喜忧参半。可能的解释包括抗细胞因子（抗-IL-5）治疗不完全耗尽嗜酸性粒细胞和/或导致症状的不可逆纤维化组织改变。
描述嗜酸性粒细胞耗竭在伴有不同嗜酸性胃肠（GI）疾病的高嗜酸性粒细胞综合征患者中的治疗效果。
对参加贝那利珠单抗（抗-IL-5RA） 2 期临床试验的一组（n=7）伴有 GI 组织嗜酸性粒细胞增多的高嗜酸性粒细胞综合征患者的血液学、组织学、内镜和临床症状进行评估，在治疗前后（NCT02130882）。
所有 GI 道节段的血液和 GI 组织嗜酸性粒细胞均完全耗尽，所有患者均报告 GI 症状改善，在某些情况下，甚至在第一个月剂量后就有改善。一些患者在没有外周或组织嗜酸性粒细胞复发的情况下出现复发性症状性发作，大多数情况下在症状缓解延长后，且在放宽饮食限制和/或减少背景治疗的情况下发生。尽管所有节段的嗜酸性粒细胞相关组织学变化均有所改善，但在复发疾病发作的患者中，食管和胃的上皮变化仍持续存在，即使在治疗 1 年后也是如此。治疗后血清类胰蛋白酶和 GI 肥大细胞通常无变化，且增加与疾病发作无关。贝那利珠单抗治疗后血清 IL-4 和 IL-5 水平升高（均 P<0.05）。
贝那利珠单抗治疗可完全耗尽伴有嗜酸性粒细胞 GI 疾病患者的血液和 GI 组织嗜酸性粒细胞，但临床反应虽令人鼓舞，但存在异质性。一些患者的残留症状可能反映了上 GI 道的持续上皮变化。
